Molecular sensors that use evanescent field interactions to detect and quantify analytes have been known for nearly two decades. Applications for such sensors include chemical and biohazard sensing, food and water testing, and biological screening for medical applications. These sensors can also be applied in research and development in academic labs (proteomics, gene studies, etc.) and for testing in the pharmaceutical industry.
A recently issued U.S. Pat. No. 7,368,281 to Mozdy et al. teaches a grating-coupled waveguide sensor system including: an evanescent-field sensor having a substrate surface with at least a parital bio- or chemo-responsive layer that forms a part of a serially renewable sensing region; an optical interrogation apparatus for monitoring the bio- or chemo-responsive layer; and an air-fluid delivery system. The substrate has reactant and non-reactant regions and can be modified with one or more materials to enhance immobilization of the bio- or chemo-responsive layer.
According to the teachings of Mozdy et al. the sensor system preferably includes a substrate with tensile strength and pliability that can be supplied from a dispensing device as a single unit in a continuous fashion; and the substrate is configurable to a fraction of its fully extended length along its longest dimension without breaking, and can be retrieved from such configuration as a continuous body suitable for performing molecular interactive assays with toxin targets. For instance, the substrate is an optically transparent (polymer) film of about 50 μm to about 2 mm thick. Alternatively, the evanescent-field sensor has a substrate in the form of a revolving platform.
Mozdy et al. in FIG. 9 graph the relationship between angle and wavelength for a particular commercial sensor. The different curves show behavior for both TE and TM polarizations for two different cover indices (water index=1.333). There is a slightly wider spread between TM modes than TE modes.
Low loss single-mode waveguides in the form of thin Silicon on insulator (SOI) substrates have been demonstrated, for example, in U.S. Pat. No. 7,315,679 to Hochberg et al. Hochberg et al. teach a system for influencing a waveguide using thin silicon structures having electrodes coupled thereto. Hochberg et al. note that it is known to provide waveguides having, a patterned silicon pathway formed on a silicon dioxide layer that is formed over a substrate. Light is substantially guided within the patterned silicon pathway. Advantageously, these waveguides can be substantially thin (e.g. from 100-200 nm, such as 120 nm). Hochberg et al. teach that the thin geometry is helpful in obtaining high field concentrations in the waveguide cladding, and that intense field concentrations in the cladding may be useful, for example, in the construction of sensors where interactions of the cladding with external stimulus perturb the propagation of light in the waveguide. The stimulus can thereby be sensed by monitoring the optical output of the waveguide. There are a wide number of sensor designs possible to leverage this principle.
In previously filed U.S. Ser. No. 11/898,660, Applicant has shown that photonic wire evanescent field (PWEF) sensors have extremely high sensitivity to molecular binding and can be made small enough that arraying many sensors on a single chip is possible.
In previously filed WO 2008/141417, Applicant teaches a thin silicon SOI sensor in which a light beam travelling in the silicon waveguide creates an evanescent optical field on the surface of the sensing element adjacent to the boundary between the sensing element and the aqueous medium. Molecular interactions occurring on this surface affect the intensity or the phase of the light beam travelling through the waveguide by changing the effective refractive index of the medium. By measuring the effect on the intensity, phase, or speed of the light beam, the molecular interactions can be detected and monitored in real time. Various configurations in which the sensor can be used, such as in a ring resonator or a Mach-Zehnder interferometer are also illustrated. In all cases the light is inserted into the waveguide at the ends of the SOI sensor.
It is also known in the art to provide diffraction based detection of analytes, for example, as taught in U.S. Pat. No. 7,008,794 to Goh. Goh teaches determining analyte presence by the presence or absence of diffraction provided by a buildup of analyte on patterned functionalization.
Other references that may be relevant include: US2006/0008206: Waveguide plate and process for its production and microtitre plate, and US20070237460: Hollow Core Optical Ring Resonator Sensor, Sensing Methods, and Methods of Fabrication.
Thin dielectric waveguides have been studied and characterized by various research programs and the intensities of evanescent fields, and the effects of propagation on cladding index, have been studied.
There remains a need for improved sensitivity and ease of interrogation of molecular sensors, especially for molecular sensors that are produced using fabrication methods that are cost efficient and compatible with mass production. Silicon photonic wire PWEF sensors have high sensitivity, and offer many possibilities for the design of extremely compact integrated optical sensor circuits that can incorporate multiple sensor arrays and correct for sensor drift due to temperature fluctuations and other variables. However initial market acceptance of PWEF sensors may be constrained by the fact that it is a very different technology than the existing label free optical sensing tools such as surface plasmon resonance (SPR). While the integrated optical fabrication and packaging technologies required to implement PWEF sensors are well established in the telecommunications industry, these technologies are unfamiliar to users and equipment manufacturers in the molecular biology, pharmaceutical and food safety sectors. Furthermore, the nature of the semiconductor manufacturing process is such that fabrication and packaging of large quantities of silicon PWEF devices can be cost effective, but initial start-up costs may still represent a barrier when a large market has not yet been established.
Therefore there is a need for a silicon biosensor chip that retains some of the advantages of silicon PWEF sensors, such as high sensitivity, but has minimal fabrication and packaging requirements, and can be interrogated using low cost off the shelf optical components in similar arrangements to those found in established technologies. The grating based sensor described here fills this need, and by design can be incorporated in existing SPR measurements systems with only minor design modifications to the SPR optical read-out system.